Altered glycosylation in host cells associated with viral infection has been reported (Ray et al. (1978) Virology 88:118; Kumarasamy et al. (1985) Arch. Biochem. Biphys. 236:593). Like oncogenesis, aberrant glycosylation induced by cytomegalovirus or by HIV causes formation of new antigens which are absent in the original host cells (Andrews et al. (1989) J. Exp. Med. 169:1347; Adachi et al. (1988) J. Exp. Med. 167:323). Using monoclonal antibodies which define oligosaccharide epitopes, appearance of Le.sup..gamma. and Le.sup..chi. antigens after viral infection has been detected.
Several studies have indicated the involvement of the carbohydrate part of HIV infection in vitro. Thus, inhibition of the early steps in Golgi glycosylation in infected cells reduces the infectivity of the virus produced (Gruters et al. (1987) Nature 330:74; Montefiori et al. (1988) PNAS 85:9248). Further, lectins block syncytium formation, probably by a specific interaction with gp 120-glycans of infected cells, and also neutralize infectivity of cell-free virus (Lifson et al. (1986) J. Exp. Med. 164:2101). Variation in N-glycosylation of target T4 cells, however, does not seem to influence HIV infection (Montefiori et al. (1988) supra).
Gp120 contains several different glycan structures, and carbohydrate constitutes 50% of the total mass of gp 120 (Matthews et al. (1987) PNAS 84:5424). Predominantly N-linked glycans have been found on gp120 (Kozaraky et al. (1989) J. Acq. Imm. Def. Syndr. 2:163). The binding site on gp120 for the T4 receptor seems to be located in a non-linear C-terminal part of the molecule (Lasky et al. (1987) Cell 50:975). Whether glycans participate directly in virus-binding is not clear. Thus, inhibitory lectins may bind to glycans adjacent to the binding site and thereby sterically interfere with T4-gp120 binding, as has been found for neutralizing antibodies (Bahraoui et al. (1988) AIDS 2:165-169; Linsley et al. (1988) J. Virol. 62:3695). Glycans so far identified on gp120 by lectin studies are ubiquitous, and the therapeutic potential of lectin-based treatment therefore seemed small.
In an article published less than 12 months before the filing date of this Application, the contents of which are incorporated herein by reference, Hansen et al (1990) J. Virol. 64:2833, disclose that three carbohydrate epitopes (A.sub.1, Le.sup..gamma., and sialosyl-Tn) were preferentially or exclusively expressed on T lymphoid cells after HIV infection. The simple mucin type structure sialosyl-Tn, as well as the related Tn and T antigens, generally are not expressed at the cell surface of normal adult cells. A humoral immune response directed to these antigens is found in cancer patients, because cancer cells may express these antigens and sensitise the immune system (Springer et al. (1979) Prog. Allergy 26:42). Hansen et al (1990) supra, disclose that antibodies directed to Tn and T did not demonstrate the presence of these antigens on HIV. This was the result of an in vitro immuno-neutralization assay, which is dependent on the special characteristics of the monoclonal antibodies used.
AIDS is recognized as a distinct new disease whose etiology has been identified as being associated with infection of a new class of lymphotrophic retrovirus termed HIV. The disease is characterized by a disorder associated with an impaired cell-mediated immunity and absolute lymphopenia, particularly reduced helper T lymphocytes (T4 or CD4). This is due to the fact that HIV preferentially infects the CD4 lymphocyte population. AIDS may be preceded by ARC, a presyndrome that is usually manifested by a complex of designated clinical features and helper T lymphopenia.
Diagnosis of infection with HIV is usually made on the basis of detecting antibodies directed against HIV. The exact antibody profile may vary with the stage of the disease (Gallo et al. (1986) Prog. Allergy 37:1).
Despite the significant advances that have been made to characterize them, methods of treating and preventing AIDS and ARC are still poorly developed. A great need exists to develop better methods for their treatment and prevention.